Brain Volume and Cognitive DeclineNovember 14, 2021
Brain Volume and Cognitive Decline
It's a cardinal feature of Alzheimer's. A shrunken brain. In fact, we have known since Rosser's Study in Neurology that the volume of the brain correlates directly with the level of cognitive function, and the rate of decline of volume is directly matched to the rate of brain shrinkage. Ok, so you want a nice, big brain. Seems obvious.
Well, it is. But we have had it backward on its etiology. We have looked at amyloid plaques and neurofibrillary tangles as the problem. They are the two pathological features you see on autopsy of Alzheimer's. They must be the cause and addressing their accumulation should be how we approach repairing or preventing Alzheimer's. Right? Actually, dead wrong. All backward.
It is impaired cognition that is toxic to the brain. First and foremost, impaired cognition comes first. Yes, I said that. It's the impaired brain function that causes everything else. When you understand this, you will then understand how to keep your brain healthy. It's actually much simpler than you think. (Little pun there).
Here is the nugget. The act of thinking, the process of activating a synapse in your brain, is absolutely defined by the secretion of acetylcholine. Period. The ability to process and make acetylcholine is the whole story. And here is the driving force: the ability to secrete choline is determined by the adequacy of plasmalogens in your synaptic membrane. That's it. You must have sufficient plasmalogens. They are the sole membrane lipids that can shapeshift, and thereby merge the neurotransmitter-containing vesicle with the synaptic membrane. It's that core function, merging with the membrane, that allows our brains to function rapidly. That function depends on plasmalogens. Adequate plasmalogens. In fact, multicellular life with neurological systems depends on those key features that plasmalogens alone have: they can shapeshift, they are the most liquid of membrane lipids, and they protect the nerve cell from oxidation with their vinyl-ether bond.
Inadequate plasmalogens set in motion a deadly and inevitable cascade. Without sufficient plasmalogens, you get insufficient secretion of acetylcholine. The nerve must function. Its only survival strategy to create acetylcholine when plasmalogen levels are inadequate is to cannibalize the synaptic membrane of choline plasmalogens. Less plasmalogen in your synaptic membranes, less fluidity, less secretion. Your plasmalogens are made with choline as an integral component. And if you don't have enough acetylcholine as a neurotransmitter, you can snitch a plasmalogen molecule from your membrane and make another acetylcholine from it. But that destroys that one plasmalogen molecule. Round and round it goes. And as that process continues to happen, the synapse collapses, shrivels up, and disappears. Each neuron has some 4,000 synapses, so you can lose one or two, but not four thousand. Lose 4000 and you have lost the neuron. Lose neurons and you have lost brain volume.
That's what comes first. The brain shrinks from the inside out, It is that simple. Without sufficient plasmalogens, you can't make sufficient acetylcholine, and your nerves can't fire. Now, what happens next? The details are then what you would expect. With the loss of a synapse, you don't need the cables of intracellular transport. Those "wires" or cables aren't needed. They pile up. We call them neurofibrillatory tangles. They didn't cause the problem, they are a marker of the problem.
And if you were paying attention, you would have intuited the means to subvert that whole deadly spiral. You need to maintain your plasmalogens. You need to maintain your choline supply in your diet. You need to maintain your neurotransmitter distribution system which is based on methylation. And you need to keep your peroxisomes healthy. That's it. Healthy plasmalogen levels can completely circumvent dementia, even the APOE4 gene. We can measure your plasmalogens and we can replace them.
Your brain has amazing resiliency and redundancy. You have many pathways to remember every word, every emotion, every map, every regret you ever had. The "Nun's Study" from Elm Grove, Wisconsin has demonstrated for us that the writing style of women, 60 years before the diagnosis of dementia, could be identified as "at risk". Losing synapses and memory isn't a 6-month affair, it is a lifetime affair. Losing a synapse here and there all adds up. Your brain always wants to rebuild resiliency and redundancy, if it has the tools. That is in your hands.
www.What will Work for me. I've measured mine, knowing my mother died of Alzheimer's. I was sort of average, maybe a tiny bit below. My risk of cognitive decline would come out to 20% or so if I did nothing. If I raise my plasmalogens up to 1 SD above the mean, I'm at 7% risk. If I raise my level to 2 SD above the mean, I'm down to 2% risk. And I've done the math. At $ 2,000 a year to replace plasmalogens, I'll spend $ 40,000 over 20 years. At age 90, I will still have a working brain and be recognizing my family. My mother, at age 90, didn't. It cost her $ 10,000 a month (in today's dollars). It's cheap to fix, compared to that.
References: Neurology, Lipids in Health and Disease, Frontier in Cell Devel Bio, Human Mol Gen, Nature, New York Times,
1. When I forget a word or overlook an errand, what might be going on? Answer: in the aggregate, the loss of some prior neuronal connection.
2. The diagnosis of Alzheimer's means what? Answer: Not covered above but likely the recognition of severe damage and impairment. On the order of 70% of synapses being lost. It's the end stage of at least a 25-year process.
3. The driving force of Alzheimer's is what? Answer: Loss of cognitive function.
4. What does that entail? Answer: Insufficient acetylcholine, driven by insufficient choline.
5. If your neuron doesn't have enough choline to make acetylcholine, what does it do? Answer: scavenges choline from plasmalogen molecules, leading to the eventual collapse of that synapse or neuron.